Oxygen-dependent biosynthetic pathways (which account for 10-20% of all oxygen utilization) are threatened by oxygen depletion, and in some cases, biosynthesis of important compounds may be sensitive to mild degrees of oxygen depletion. In order to further characterize the effects of oxygen depletion on these oxygen-dependent reactions, representative oxygen-dependent cellular processes (tryptophan catabolism; prolyl hydroxylation) will be investigated in tissue culture models in order to determine: 1. The degree of oxygen depletion required to impair these processes. 2. The nature of the cellular response to threatened impairment of these reactions. Content and activity of oxygen-dependent enzymes catalyzing these reactions will be determined to investigate whether cells regulate enzyme activity and enzyme content in response to oxygen depletion. 3. The mechanism by which oxygen regulates enzyme content will be investigated by determining the rate of synthesis and degradation of these enzymes.